Antibodies directed against ICOS and uses thereof

Abstract

The present invention provides antibodies directed against ICOS or a derivative thereof which neutralize ICOS engagement on Treg by inhibiting the fixation between ICOS and ICOS-L and abrogate proliferation of Treg induced by plasmacytoid dendritic cells. The present invention further provides antibodies directed against ICOS or a derivative thereof which induce IL-10 and IFNγ production, induce CD4− T cells proliferation, reduce Tconv proliferation, and increase the immunosuppressive function of Treg.

The invention claimed is: 
     
       1. An antibody directed against ICOS which increases the immunosuppressive function of regulatory T cells, wherein said antibody comprises a CDRH3 comprising the sequence set forth in SEQ ID NO:25, or a CDRH3 comprising no more than three amino acid substitutions in the sequence set forth in SEQ ID NO:25. 
     
     
       2. An antibody directed against ICOS, wherein said antibody is selected from the group consisting of Icos 53-3, Icos 88-2 and Icos 92-17, respectively obtainable from the hybridoma deposited at the CNCM on Jul. 2, 2009 under the accession numbers CNCM I-4176, CNCM I-4177, and CNCM I-4178. 
     
     
       3. An antibody directed against ICOS, wherein said antibody has the following 6 CDRs:
 H-CDR1 of amino acid sequence GYSFTSYWIN (SEQ ID NO:23); 
 H-CDR2 of amino acid sequence NIYPSDSYTNYNQMFKD (SEQ ID NO:24); 
 H-CDR3 of amino acid sequence WNLSYYFDNNYYLDY (SEQ ID NO:25); 
 L-CDR1 of amino acid sequence RSSKSLLHSNGNTYLY (SEQ ID NO:26); 
 L-CDR2 of amino acid sequence RMSNLAS (SEQ ID NO:27); and 
 L-CDR3 of amino acid sequence MQHLEYPWT (SEQ ID NO:28). 
 
     
     
       4. An antibody according to  claim 3 , wherein the nucleotidic sequences encoding the 6 CDRs are the following:
 H-CDR1: GGCTACAGTTTCACCAGCTACTGGATAAAC (SEQ ID NO:17); 
 H-CDR2: AATATTTATCCTTCTGATAGTTATACTAACTACAATCAAA TGTTCAAGGAC (SEQ ID NO:18); 
 H-CDR3: TGGAATCTTTCTTATTACTTCGATAATAACTACTACTTGG ACTAC (SEQ ID NO:19); 
 L-CDR1: AGGTCTAGTAAGAGTCTCCTGCATAGTAATGGCAACACT TACTTGTAT (SEQ ID NO:20); 
 L-CDR2: CGGATGTCCAACCTTGCCTCA (SEQ ID NO:21); 
 L-CDR3: ATGCAACATCTAGAATATCCGTGGACG (SEQ ID NO:22). 
 
     
     
       5. A method of treatment comprising administering an effective amount of the antibody according to  claim 1  to a patient suffering from a disease selected from the group consisting of autoimmune diseases, transplantation rejection or a graft versus host disease. 
     
     
       6. A method of treatment comprising administering an effective amount of the antibody according to  claim 1  to a patient suffering from an inflammatory disorder. 
     
     
       7. The method according to  claim 6 , wherein said patient suffers from an inflammatory disorder selected in the group consisting of inflammatory disorder of the nervous system, mucosal inflammatory disease, inflammatory skin disease and autoimmune arthritis. 
     
     
       8. The method according to  claim 6 , wherein said patient suffers from an inflammatory disorder selected from multiple sclerosis, inflammatory bowel disease, asthma or tonsillitis, dermatitis, psoriasis, contact hypersensitivity and rheumatoid arthritis.